We attempt to simulate the DA release that they may be initiated by a number of environmental or other stimuli, as hypothesized by Grace and others. Recently, studies by Laruelle et al. have suggested a significant increase in DA release on average in SCZ as compared with normal controls using SPECT. We employed the same amphetamine dose as Laruelle, but our studies differ in 2 ways. First, ours is a bolus rather than continuous infusion method using PET and [11C]raclopride. Second, because of the design of some of our studies (See specific Aim 2 below) the DA release may also be augmented by low specific activity raclopride. Using several different methods involving a radioactive plasma input function and kinetic models or simple time activity curves, we observed a similar trend to that of Laruelle trend of elevated DA release, Figure 1, although not as marked. In schizophrenic subjects for whom we were able to perform 4 scans including low specific activity raclopride, there appears to be a trend for a greater difference in the dopamine surge compared to normals. The average % DA release is numerically larger for schizophrenic patients but the sample size and variance is still too great to reach any conclusions. Additional refinement, subtyping or analyses and more subjects are needed. We have also tried to maximize our ability to detect the difference between patients with SCZ and normals by modifying the timing of the bolus IV AMP given relative to the IV bolus [11C]raclopride.